Electrostatic actuation for management of flow in micro-total analysis systems (μ-TAS) and related method thereof

ABSTRACT

The present invention relates to microfluidic devices, and in particular, flow management in such devices. In particular, the present invention provides an electrostatic valve for flow manipulation in a microfluidic device. The valve of the present invention sits on a valve seat in a microchannel and deflects away from the valve seat by electrostatic actuation to assume an opened configuration to allow fluid flow.

RELATED METHOD THEREOF

This application claims the priority of U.S. Provisional PatentApplication Ser. No. 60/618,127, filed Oct. 13, 2004, the disclosure ofwhich is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to microfluidic devices, and inparticular, flow management in such devices.

BACKGROUND OF THE INVENTION

Miniaturization of analytical methodology onto microdevices has seen asurge of research interest over the recent decade due to thepossibilities of reduced reagent and sample volumes, reduced analysistimes, and parallel processing. Another leading advantage ofminiaturization is the potential to integrate multiple sample handlingsteps with analysis steps to achieve integrated, user-friendly,sample-in/answer-out devices—commonly referred to asmicro-total-analysis systems (μ-TAS). Many of these emerging μ-TAS cansimply be interfaced with a computer for automated, user-friendlyapplications.

Microfluidic devices are known. For example, U.S. Pat. Nos. 6,130,098 toHandique; 6,919,046 to O'Connor et al.; 6,544,734 to Briscoe et al.; thedisclosures of which are incorporated herein by reference, disclosesmicrofluidic devices for use in biological and/or chemical analysis. Thesystem includes a variety of microscale components for processingfluids, including reaction chambers, electrophoresis modules,microchannels, detectors, valves, and mixers. Typically, these elementsare microfabricated from silicon, glass, ceramic, polymer, metal, and/orquartz substrates. The various fluid-processing components are linked bymicrochannels, through which the fluid flows under the control of afluid propulsion mechanism. If the substrate is formed from silicon,electronic components may be fabricated on the same substrate, allowingsensors and controlling circuitry to be incorporated in the same device.These components can be made using conventional photolithographictechniques, as well as with laser ablation, polymer molding, hotembossing, micromachining, physical/mechanical removal, or similarmethods. Multi-component devices can be readily assembled into complex,integrated systems. In most microfluidic research laboratories,photolithography and chemical etching are used in their simplest form tocreate patterns in a monolithic configuration.

A large breadth of biological and/or chemical analyses is possible withmicrodevices having multifunction capabilities. The key to creatingmultifunctional devices with turn-key operation capability will be theintegration of processes for total analysis. For example, for genomicanalysis, the totally integrated analysis would require that steps suchas cell lysis, DNA extraction, DNA purification, and DNA amplification(via PCR) be carried out on-chip prior to electrophoresis on the samemicrodevice. This promises to provide investigators with a powerfultechnology that will minimize sample and operator contamination, as wellas reduce the potential for concomitant error often induced by sampletransfer and the interchange between devices. Other advantages includecircumventing the need for large sample volumes (many systems requireonly nanoliter volumes) and increasing reaction rates (Manz et al. Adv.Chromatogr. 1993, 33:61).

One of the important issues for proper function of a μ-TAS is thecontrol of fluid flow through the microfluidic network of the device.Each compartment or microscale component of the device is connected toanother through a microchannel that facilitates the transfer of samplefrom one location in the microdevice to the next. Moreover, while thevarious functionalities on the chip are connected by their inherentdependency on one another, they are, nonetheless, independent unitscarrying out very different chemistries. In fact, the reagentsused/contained in any functional domain are often harmful to theprocesses carried out in other domains. For example, isopropanol andguanidine are critical for the extraction of DNA from cell lysates;however, leakage of either reagents into a PCR domain (one possiblepathway in the sample preparation sequence) is fatal to theamplification process (inhibits PCR). As a result, keeping the variousdomains connected but chemically isolated is a necessity. In morecomplicated microdevices, this is accomplished with a system of ‘pumps’and ‘valves’ to control and direct flow from one compartment to thenext.

The mechanisms of valve actuation are manifold. Some rely on pneumaticmechanism while others depend upon mechanical pressure or piezoelectricmethods. Many systems rely on a flexible, elastomer valve (Unger et al.Science 2000, 288:113; Grover et al. Sens. Actuators B 2003, 89:315)that can be easily manipulated so as to allow on-command distension,while others have utilized pH-sensitive (Yu et al. Phys. Lett. 2001,78:2589) or thermo-reactive polymers (Harmon et al. Polymer 2003,44:4547; Yu et al. Anal. Chem. 2003, 75:1958). Olefins (Klintberg etal., Sens. Actuators A 2003, 103:307; Selvaganapathy et al. Sens.Actuators A 2003, 104:275), ferro-fluid (Hatch et al. J.Microelectromechan. Syst. 2001, 10:215), and air bubbles (Song et al. J.Micromech. Microeng. 2001, 11:713; Handique et al. Anal. Chem. 2001,73:1831; U.S. Pat. No. 6,877,528 to Gilbert et al.) have also been usedfor valving. Additionally, a number of mechanisms exist for generatingflow through the microchannels. The method of Unger et al. starts withall valves in the open position, and then, in a stepwise fashion, eachvalve closes in series (via pressure actuation) to create a peristalticpump. Another method by Grover et al. functions similarly to adiaphragm. All valves start in the closed position and flow isaccomplished by successive opening (via pneumatic mechanisms) of valvesin a determined pattern. Both the Unger et al. and Grover et al. methodsuse solenoid valves coupled directly into the channel wall and require aseparate pump to operate.

Other prior art valves for use in microfluidic devices include U.S. Pat.Nos. 6,901,949 and 6,817,373 to Cox et al.; 6,802,489 to Marr et al.;6,783,992 to Robotti et al.; 6,748,975 to Hartshorne et al.; 6,698,454to Sjolander et al.; 6,615,856 to McNeely et al.; 6,581,899 to Williams;6,561,224 to Cho; 6,431,212 to Hayenga et al.; and 6,382,254 to Yang etal.; the disclosures of which are incorporated herein by reference.

As with most methods used for directing flow through a microchannelnetwork, the prior art valves are not without limitations, which includeinefficient flow control, large power requirements, slow response speed,size, portability challenge and restrictions associated with thechemical characteristics of the elastomer as it pertains to theapplication. Consequently, there is a critical need to develop totallyintegrated microfluidic devices with valving capabilities that not onlymeet the needs of the application in a cost-effective manner, but alsoallow for simple, smooth, and precise control of flow through themicrochannel architecture.

SUMMARY OF THE INVENTION

An object of the present invention is to provide an electrostatic valvefor flow manipulation in a microfluidic device. Specifically, it relatesto management of fluid flow in micro total analysis systems through theuse of an elastomer valve. An advantage of some of the embodiments ofthe current invention is the ability to control flow using mechanismsspecific to flow control, which are independent of the fluidic network.Other advantages include improved portability, greater control of flowrates, increased response speed, reduced device size, and smaller powerrequirements. Some of the embodiments of the current invention alsoallow the use of any type of elastomer valve to manipulate flow througha microchannel.

In one aspect of the present invention, the valve contains a valve filmcoated with a conductive material overlaying a valve seat on amicrofluidic substrate having at least a microscale component therein.Above the coated film and the valve seat is an electrode separated fromthe coated film by a gap. When the coated film is seated directly on topof the valve seat, fluid flow across the valve seat is prevented.However, when an electrical potential is applied between the electrodeand the conductive coating of the film, attraction between the film andelectrode causes the film to lift away from the valve seat, allowing forfluid to flow across the valve seat in the space between the film andthe valve seat.

In another aspect of the present invention, the valve contains a firstfilm overlaying a valve seat on a microfluidic substrate having at leasta microscale component therein. The first (valve) film, on the sidefacing away from the microfluidic substrate, is fluidly connected withand is fluidly connected to a fluid reservoir containing a fluid.“Fluidly connected” as used herein refers to a condition wherein twoelements are connected to each other by or in contact with the samecontinuous body of fluid. The fluid reservoir is covered by a second(actuator) film coated with a conductive material. Above the second filmsits an electrode separated from the coated film by a gap. Because thesecond film is physically removed from the first film, the physicalparameters controlling electrostatic actuation can be adjustedindependently of the flow requirements of the channel. In this manner,the relative motion of both films can be different, such that one canachieve large valve motion in the first (valve) film with smalldisplacements of the second (actuator) film.

To achieve this amplification of actuator displacement, the area of thereservoir that is fluidly connected with the second film must be greaterthan the area of the reservoir that is in fluid contact with the firstfilm. When an electrical potential is applied between the electrode andthe conductive coating of the film, attraction between the second filmand electrode causes the second film to lift away from the fluidreservoir, which causes the first film to lift a way from the valveseat, because the fluid reservoir is full of fluid and both first andsecond films are in fluid contact with each other. In thisconfiguration, a small amplitude of deflection of the second film, uponapplication of an electrical potential between the second film and theelectrode, causes a greater amplitude of deflection in the film seatedon the valve seat, allowing a larger fluid path between the film and thevalve seat.

Another object of the present invention is to provide methods of makinga microfluidic device containing the electrostatic valve of the presentinvention.

Yet another object of the present invention is to provide methods ofconducting biological and/or chemical analysis in an integratedmicrofluidic device using the electrostatic valve of the presentinvention.

Electrostatic actuation for management of flow in micro total analysissystems can be performed for all steps in any biological and/or chemicalanalysis known to exist. These include, but are not limited to, geneticassays, DNA sequencing, protein detection, chromatography, PCR, highthroughput screening, and the like.

An advantage of some of the embodiments of the current invention is theability to control flow independent of the fluidic network. Otheradvantages include improved portability, greater control of flow rates,increased response speed, reduced device size, and smaller powerrequirements. Some of the embodiments of the current invention can befabricated with a wide range of polymeric materials (including thosethan can be spin-coated from solution). A novel concept is, among otherthings, the generation of large actuator displacements (on the scale oftens of microns) using an independent electrostatic gap that can be muchsmaller, significantly reducing actuation voltages. The novel approachcombines microfluidic reservoirs and electrostatic actuation, and isapplicable to any micro-device where large displacements are required. Afeature of the design is to choose actuator dimensions independentlyfrom the component being deformed, which greatly broadens the range ofmoveable component dimensions and performance.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram showing the electrostatic valve design of the firstembodiment of the present invention.

FIG. 2 is a diagram showing the electrostatic valve design of the secondembodiment of the present invention.

FIG. 3 is a top view showing multiple valves each connected to a fluidreservoir by a channel.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Microfluidic devices typically include micromachined fluid networks.Fluid samples and reagents are brought into the device through entryports and transported through channels to a reaction chamber, such as athermally controlled reactor where mixing and reactions (e.g.,synthesis, labeling, energy-producing reactions, assays, separations, orbiochemical reactions) occur. The biochemical products may then bemoved, for example, to an analysis module, where data is collected by adetector and transmitted to a recording instrument. The fluidic andelectronic components are preferably designed to be fully compatible infunction and construction with the reactions and reagents.

There are many formats, materials, and size scales for constructingmicrofluidic devices. Common microfluidic devices are disclosed in U.S.Pat. Nos. 6,692,700 to Handique et al.: U.S. Pat. No. 6,919,046 toO'Connor et al.; 6,551,841 to Wilding et al.; 6,630,353 to Parce et al.;6,620,625 to Wolk et al.; and 6,517,234 to Kopf-Sill et al.; thedisclosures of which are incorporated herein by reference. Typically, amicrofluidic device is made up of two or more substrates that are bondedtogether. Microscale components for processing fluids are disposed on asurface of one or more of the substrates. These microscale componentsinclude, but are not limited to, reaction chambers, electrophoresismodules, microchannels, fluid reservoirs, detectors, valves, or mixers.When the substrates are bonded together, the microscale components areenclosed and sandwiched between the substrates. In many embodiments,inlet and outlet ports are engineered into the device for introductionand removal of fluid from the system. The microscale components can belinked together to form a fluid network for chemical and/or biologicalanalysis. Those skilled in the art will recognize that substratescomposed of silicon, glass, ceramics, polymers, metals, and/or quartzare all acceptable in the context of the present invention. Further, thedesign and construction of the microfluidic network vary depending onthe analysis being performed and are within the ability of those skilledin the art.

A first embodiment of the present invention is depicted in FIG. 1. Afirst substrate 2 contains a microchannel 4, having a fluid flowing inthe direction of the arrow. The flow is controlled by a valve containinga film 6 coated with an electrically conductive layer 8, and a valveseat 16. The valve seat 16 is constructed such that when the film 6 sitsdirectly on the valve seat 16, fluid flow across the valve seat isprevent, but when the film 6 is lifted from the valve seat 16, fluid canflow over the valve seat 16 in the space between the valve seat 16 andthe film 6. Above the film is a second substrate 10 having a fixedelectrode 12 and a gap 14 dispose therein. The second substrate 10 isdirectly above the film 6, such that the conductive coating 8 of thefilm 6 is separated from the electrode 12 by the gap 14 and locatesdirectly below the gap. When the film 6 sits directly on top of thevalve seat 16, flow across the valve seat 16 is inhibited. This positionis referred to as the closed position. When an electrical potential isapplied between the conductive coating 8 and the electrode 12,electrostatic attraction between the conductive coating 8 and electrode12 causes the film to lift away from the valve seat 16 (the lifting ofthe valve from the valve seat 16 is depicted as dashed lines in FIG. 1),which allows fluid to flow across the valve seat through the openingbetween the valve seat 16 and the film 6 (the direction of fluid flow isdepicted in FIG. 1 as dashed arrow). The position in which the valvelifts away from the valve seat is referred to herein as the openedposition.

Although FIG. 1 depicts the valve seat 16 below the valve film 6, oneskilled in the art would understand that the position could easily bereversed where the film is below the valve seat. In this position, theopened position results from deflection of the film downward rather thanupward. This configuration is essentially FIG. 1 turned upside down.

Moreover, one skilled in the art would understand that deflection of thefilm could result in closing rather than opening of the valve; and suchdesign would be apparent to one skilled in the art. For example, one canenvision a configuration where the valve seat and coated film is locatedabove the microchannel and the electrode is on the bottom of themicrochannel such that when actuated, the membrane deflects toward thebottom of the microchannel to shut off flow in the channel. In thisconfiguration, actuation results in closing rather than opening of thechannel.

In order to allow for significant flow rates, the valve displacement(into the electrostatic gap 14) must scale with the microchannel 4dimensions. For devices with typical channel heights on the order of 100μm, the required electrostatic gap size, A, is even larger than thedesired valve displacement. Since the operating voltage scales with1/Δ²≈1/h_(c) ² (where h_(c) is the channel height), film deflection onthe order of 10 μm and valve films with thickness on the order of 100 μmtranslate into operating voltages in the kV range, which creates manydifficulties.

In a second embodiment, the present inventors have overcome thesedifficulties by providing an integrated electrostatic microfluidicactuator wherein an isolated fluid reservoir couples the input andoutput displacements of the valve. The underlying concept behind theapproach is illustrated in FIG. 2. In this embodiment, there are twofilms, a first (valve) film 100 directly seated on the valve and asecond (actuator) film 102 covering a fluid reservoir 104. The firstfilm 100 sits on top of a microchannel 106 of a first substrate 108. Themicrochannel has a valve seat 110 therein to control fluid flow. The topside (the side not in contact with the valve seat) of the first film 100that is directly above the valve seat 100 is in fluid contact with thefluid reservoir 104. The top of the fluid reservoir 14 is covered withthe second film 102 that is coated with a conductive material 112. Theconductive material is separated from a fixed electrode 114 by a gap 116with a separation distance Δ. The top surface of the fluid reservoir 104that is covered by the second film 102 must be larger to amplify thedisplacements of the valve film 100; that is, if the span of theactuator film 102 is larger than the span of the valve 100, thedisplacement of the valve 100 will be greater than that of the actuatorfilm 102. The ratio between actuator film displacement and that of thevalve film scales with the square of the ratio of their spans; that is,if the actuator span 102 is ten times larger than the span of the valve,the displacement of the valve 100 will be one hundred times larger thanthe actuator film displacement. For most microfluidic valveapplications, this implies that the actuator film should be 5-100 timeslarger than the valve film, such that relative small actuatordisplacements yield large output (valve displacement).

The fluid reservoir is filled with a fluid such that the first andsecond films 102 and 100 are fluidly connected. When a electricalpotential is actuated between the conductive coating 112 and the fixedelectrode 114, electrostatic attraction between the conductive coating112 and the fixed electrode 114 causes the film to deflect away from thetop of the fluid reservoir 104 toward the fixed electrode 114 (seedashed line) by a distance δ₂. Because the fluid reservoir 104 is filledwith the fluid and the two films 100 and 102 are in fluid contact, thefirst film 100 also deflects away from the valve seat 110, by a distanceδ₁, to allow flow across the valve seat 110 in the space between thefirst film 100 and the valve seat 110. In this embodiment, because thetop surface of the fluid reservoir 104 that is covered by the secondfilm 102 is larger than the area of the fluid reservoir that is fluidlyconnected to the first film 100, the fluid reservoir transmits theactuation pressure generated over a relatively large area to an outputfilm (the first film 100) that is much smaller. The electrostatic gap116 is placed outside the fluid chamber, and is thus decoupled from theheight of the microchannel 106. The volume displaced by the smallactuator displacement (δ₂) over a large area is accommodated by largedisplacement (δ₁) of the output valve over a small area.

Although FIG. 2 shows the fluid reservoir 104 directly above the firstfilm 100, this needs not be so. The first film 100 needs only be fluidlyconnected with the fluid reservoir 104 and the second film (102). Thiscan also be accomplished, for example, through a microchannel thatconnects the first film 100 to the fluid reservoir 104. In this case,the fluid reservoir 104, however, needs not be in the vicinity of thefirst film 100. It is important, however, that the films 100 and 102 arefluidly connected, which means that the fluid reservoir 104 and thechannel connecting the fluid reservoir 104 to the first film must befilled with the fluid. If a fluid is used in the reservoir chamber, thefluid reservoir does not need to be adjacent to the valve film, becausefluidic pressure will be transmitted through any connected microchannelsystem. This is an important advantage of the present embodiment,because it provides an approach to physically separate the actuator filmand the valve, i.e. the actuator film can be placed in a differentlocation than the valve, as long as they are fluidly connected.

A series of valves can be placed on a microfluidic device forcontrolling the flow of fluid with in a microchannel or betweenmicroscale components of a microfluidic device. An example of this isshown in FIG. 3, which shows a top view of three valves 500 along amicrochannel 502 for control fluid flow. The valves can be controlledindependently by having each valve being associated with a separatefixed electrode. Further, the fluid reservoirs 504 are not directly ontop of the valve, but are fluidly connected to its corresponding valveby a channel 506. Preferably, the reservoirs also have inlet and outletchannels 508 and 510, respectively, for filling and withdrawing fluidsfrom the reservoirs.

The film of the present invention is preferably an elastomeric polymersimilar to the elastomeric valves disclosed in U.S. Patent ApplicationPublication Nos. 2005/0166980 and 2002/0109114, the disclosures of whichare incorporated herein by reference. In general, elastomers deform whenforce is applied, but then return to their original shape when the forceis removed. The elasticity exhibited by elastomeric materials may becharacterized by a Young's modulus. Elastomeric materials having aYoung's modulus of between about 10 kPa-10 GPa, preferably between about100 kPa-500 MPa, more preferably between about 300 kPa-100 MPa, and mostpreferably between about 500 kPa-10 MPa are appropriate for the presentinvention, although elastomeric materials having a Young's modulusoutside of these ranges could also be utilized depending upon the needsof a particular application. Many types of elastomeric polymers can beuseful in for the valve of the present invention, which include, but arenot limited to, polyisoprene, polybutadiene, polychloroprene,polyisobutylene, poly(styrene-butadiene-styrene), the polyurethanes, andsilicone polymers; or poly(bis(fluoroalkoxy)phosphazene) (PNF, Eypel-F),poly(carborane-siloxanes) (Dexsil), poly(acrylonitrile-butadiene)(nitrile rubber), poly(1-butene),poly(chlorotrifluoroethylene-vinylidene fluoride) copolymers (Kel-F),poly(ethyl vinyl ether), poly(vinylidene fluoride), poly(vinylidenefluoride-hexafluoropropylene)copolymer (Viton), elastomeric compositionsof polyvinylchloride (PVC), polysulfone, polycarbonate,polymethylmethacrylate (PMMA), polytetrafluoroethylene (Teflon),polydimethylsiloxane (PDMS), and blends thereof.

The fluid used to fluidly connect the two films can be any fluid,preferably a substantially incompressible fluid; however, the viscosity(and elasticity, if any) of the fluid is important in transmitting theinput displacement of the second film to the valve. The speed oftransmission depends on the distance between the fluid reservoir and thevalve and the viscosity of the fluid. The longer the distance betweenthe fluid reservoir and the valve, the lower the viscosity of the fluidrequired to maintain the same transmission speed. Thus, if the fluidreservoir is directly on top of the valve as shown in FIG. 2, then thefluid can be more viscous. On the other hand, if the fluid reservoir isfurther from the valve, e.g. as shown in FIG. 3, then a lower viscosityfluid is required. Generally, the dynamic viscosity of the fluid ispreferably about 0.0001-2 Ns/m², more preferably about 0.001-0.01 Ns/m²,and most preferably about 0.0001-0.001 Ns/m².

It must be noted, however, that the ability to transmit pressures via aviscous (or viscoelastic) substance is governed by the shear transferthat occurs between the side walls and the fluid in the channel, whichis influenced by both the viscosity and any elastic response of thematerial, as well as the dimensions of the reservoir. If the substanceis a true fluid (such that it cannot support any static shear stress,i.e. the elastic response is negligible—such as water or completelyuncrosslinked polymers), then the viscosity of the fluid merely willaffect the time response. However, if the fluid has an elastic component(such as occurs in partially cross-linked polymers), then shear transferimplies that compressive stresses build in the channel and limit output.Therefore, substances with partially elastic response, such ascross-linked polymers or gels, are highly undesirable for the presentinvention. The following fluids are appropriate for the presentinvention (depending on the choice of the valve/actuator films whichseal the chamber): aqueous/organic liquids, aqueous solutions containinguncross-linked polymers, and any other immiscible fluids (includingoils). Aqueous solutions preferably are those functioning asphysiological buffers, high ionic strength solutions, includingchaotropes, and containing uncross-linked polymers. Organic liquids arepreferably alcohols, such as isopropanol, methanols, ethanols, andsynthetic organic fluids, such as hexanes, dimethyl formamide, anddimethyl sulfoxide.

Most conductive coatings are appropriate for the present invention. Itis most desirable that the conductive coating is compatible with thefilm and does not affect its elastomeric properties. Preferredconductive coatings are, but are not limited to, metals (such asaluminum, copper, gold, or chromium), and conductive polymers (such aspolypyrrole, polyaniline, or poly-divinyl fluoride). It is not importantthat the conductive film covers the entire surface area of the valvefilm. As such, micro-patterned grids, lines, zig-zags, etc. ofconductive material will allow for device function, and may be preferredin some applications where large actuator film compliance is desired.

The construction of the present invention can be made using currentlyavailable techniques, such as etching, laser ablation, polymer molding,hot embossing, micromachining, etc. Preferably, the devices are made bythe bonding of at least two substrates. For example, the firstembodiment (FIG. 1) is preferably made from two substrates: a firstsubstrate 2 having microfluidic channels 4, valve seats 16, and a coatedfilms 6 disposed thereon; and a second substrate 10 having fixedelectrodes 12 and gaps 14 disposed thereon. The microfluidic device isformed when the two substrates are bonded together forming amicrofluidic network having electrostatic valves for controlling theflow of liquid.

The second embodiment (FIG. 2) is preferably made with substrates: afirst substrate 108 having microfluidic channels 106, valve seats 110,and first (valve) films 100 disposed thereon; a second substrate 118having fluid reservoirs 104, channels connecting the fluid reservoirs tothe valve, and second (coated) film disposed thereon; and a thirdsubstrate 120 having fixed electrodes 114 and gaps 116 disposed thereon.The microfluidic device of FIG. 2 is formed when the three substratesare bonded together forming a microfluidic network having electrostaticvalves for controlling the flow of liquid.

The second embodiments of the invention can be assembled according tothe following plan:

The device is divided into two parts: a fluid reservoir and anelectrostatic actuated freestanding span (the valve). These parts arethen mechanically assembled to create a high displacement valve withrelatively low operating voltages.

The fluid reservoir consists of three layers fabricated throughsuccessive applications of SU-8 (photoresist) with selective exposureand a single development. The first layer's purpose is to set the radiusof the lower span (the valve). The first layer is constructed on an SU-8release layer so that the entire device can be removed from thesubstrate and integrated into another system. The thickness of thislayer can either be increased to offer great rigidity for mechanicalassembly or reduced to minimize reservoir volume (˜50 μm). The secondlayer has two microchannels used to transport fluid into the reservoir.The third layer provides the upper wall to the micro-channels as well assurface access to the channels. The main chamber of the reservoir isshared between the second and third layers and the radius of the upperactuating span sets its dimensions. The second layer must be thick (˜75μm) due to the fact that some of the some of the uncured SU-8 in thechannels will harden with the application and exposure of the third SU-8layer. Previous experiments have shown that approximately 25 μm willbecome cured, reducing the channel depth to 50 μm. This should allow foradequate flow when filling the chamber. The third layer is approximately10 μm thick. Increasing its thickness would require longer exposuretimes that may reduce the height of the channels. This gives the fluidreservoir a total thickness of approximately 135 μm, which is suitablefor mechanical assembly. After all three layers have been patterned thereservoir is developed in an ultrasonic bath of PGMEA to remove theuncured SU-8 in the channels and reservoir chamber.

The electrostatic portion of the device consists of a base electrode anda freestanding PDMS film suspended on an SU-8 platform. First, theelectrode is deposited on to a substrate (preferably glass to easealignment). This is accomplished by spinning and patterning a thicklayer of photo resist and then depositing a layer of Cr/Au (50 nm/50nm). The photo resist is then removed in an acetone ultra-sonic bathleaving the desired gold pattern. An SU-8 layer is then spun on andpatterned but not developed. This creates a hard platform for theactuator span to rest on and also leaves a sacrificial layer of uncuredSU-8 on which to spin a thin layer of PDMS (˜10 um). After the PDMSlayer is spun on the uncured SU-8 is removed via channels through theplatform creating a freestanding film. An electrode is then patternedonto the film using the same lift-off process described above. Analternative to this method would be to pattern the base electrode andSU-8 platform then mechanically adhere the PDMS film. However, thislimits the span thickness that can be used due to the difficulty ofhandling and aligning thin polymer films.

After both components are finished the electrostatic device is invertedand adhered to the fluid reservoir. The reservoir substrate is thenremoved leaving an opening at the base. This entire device can then befilled with fluid and adhered to the film to be actuated.

The systems described herein generally include microfluidic devices, asdescribed above, in conjunction with additional instrumentation forcontrolling fluid transport, flow rate and direction within the devices,detection instrumentation for detecting or sensing results of theoperations performed by the system, processors, e.g., computers, forinstructing the controlling instrumentation in accordance withpreprogrammed instructions, receiving data from the detectioninstrumentation, and for analyzing, storing and interpreting the data,and providing the data and interpretations in a readily accessiblereporting format. The controller system can also be coupled to anappropriately programmed processor or computer which functions toinstruct the operation of these instruments in accordance withpreprogrammed or user input instructions, receive data and informationfrom these instruments, and interpret, manipulate and report thisinformation to the user. As such, the computer is typicallyappropriately coupled to one or both of these instruments (e.g.,including an analog to digital or digital to analog converter asneeded).

The computer typically includes appropriate software for receiving userinstructions, either in the form of user input into a set parameterfields, e.g., in a user interface, or in the form of preprogrammedinstructions, e.g., preprogrammed for a variety of different specificoperations. The software then converts these instructions to appropriatelanguage for instructing the operation of the fluid direction andtransport controller to carry out the desired sequential actuation ofthe valves. The computer may also receive the data from the one or moresensors/detectors included within the system, and interpret the data,either in a user understood format or using that data to initiatefurther controller instructions, in accordance with the programming,e.g., such as in monitoring and control of flow rates, temperatures,applied voltages, and the like.

Although certain presently preferred embodiments of the invention havebeen specifically described herein, it will be apparent to those skilledin the art to which the invention pertains that variations andmodifications of the various embodiments shown and described herein maybe made without departing from the spirit and scope of the invention.Accordingly, it is intended that the invention be limited only to theextent required by the appended claims and the applicable rules of law.

1. A system for controlling fluid flow in a microfluidic devicecomprising a microchannel having a valve seat therein; a valve filmoverlaying the valve seat so as to block fluid flow when the film isseated directly on top of the valve seat; and a mechanism for deflectingthe film away from the valve seat upon actuation, the mechanismcomprising: a fluid reservoir fluidly connected to the valve film, anactuator film having a conductive coating thereon covering an opening ofthe fluid reservoir, wherein the actuator and the valve films arefluidly connected; and a fixed electrode opposing and separated from theconductive coating by a gap.
 2. The system of claim 1, wherein theconductive coating is a continuous blanket coating or is patterned bymicro-fabrication.
 3. The system of claim 1, wherein the fluid reservoiris fluidly connected to the valve film by a channel.
 4. The system ofclaim 1, wherein the fluid reservoir is placed in a different physicallocation than the valve film to physically separate the location of theactuator film and valve film, and fluidly connected to both the actuatorfilm and the valve film by fluidic channels.
 5. The system of claim 1,wherein inlet and outlet channels are connected to the fluid reservoir.6. The system of claim 1, wherein the fluid reservoir is hermeticallysealed.
 7. The system of claim 1, wherein the area of the fluidreservoir covered by the coated film is larger than the area of thefluid reservoir that is in direct fluid contact with the first film. 8.The system of claim 1, wherein at least one of the actuator film or thevalve film is made of an elastomeric polymer.
 9. The system of claim 8,wherein the elastomeric polymer is selected from the group consisting ofpolyisoprene, polybutadiene, polychloroprene, polyisobutylene,poly(styrene-butadiene-styrene), the polyurethanes, and siliconepolymers; or poly(bis(fluoroalkoxy)phosphazene),poly(carborane-siloxanes), poly(acrylonitrile-butadiene),poly(1-butene), poly(chlorotrifluoroethylene-vinylidene fluoride)copolymers, poly(ethyl vinyl ether), poly(vinylidene fluoride),poly(vinylidene fluoride-hexafluoropropylene)copolymer, elastomericcompositions of polyvinylchloride (PVC), polysulfone, polycarbonate,polymethylmethacrylate (PMMA), polytetrafluoroethylene,polydimethylsiloxane (PDMS), and blends thereof.
 10. A method forcontrolling fluid flow in a microfluidic device comprising: providing amicrochannel having a valve seat therein; providing a film overlayingthe valve seat so as to block fluid flow when the film is seateddirectly on top of the valve seat; and providing a mechanism fordeflecting the film away from the valve seat upon actuation, themechanism comprising: a fluid reservoir fluidly connected to the valvefilm, an actuator film having a conductive coating thereon covering anopening of the fluid reservoir, wherein the actuator and the valve filmsare fluidly connected; and a fixed electrode opposing and separated fromthe conductive coating by a gap; and actuating or deactuating themechanism to allow or to retard flow.
 11. The method of claim 10,wherein the conductive coating is a continuous blanket coating or ispatterned by micro-fabrication.
 12. The method of claim 10, wherein thefluid reservoir is fluidly connected to the valve film by a channel. 13.The method of claim 10, wherein the fluid reservoir is placed in adifferent physical location than the valve film to physically separatethe location of the actuator film and valve film, and fluidly connectedto both the actuator film and the valve film by fluidic channels. 14.The method of claim 10, wherein inlet and outlet channels are connectedto the fluid reservoir.
 15. The method of claim 10, wherein the fluidreservoir is hermetically sealed.
 16. The method of claim 10, whereinthe area of the fluid reservoir covered by the coated film is largerthan the area of the fluid reservoir that is in direct fluid contactwith the first film.
 17. The method of claim 10, wherein at least one ofthe actuator film or the valve film is made of an elastomeric polymer.18. The method of claim 17, wherein the elastomeric polymer is selectedfrom the group consisting of polyisoprene, polybutadiene,polychloroprene, polyisobutylene, poly(styrene-butadiene-styrene), thepolyurethanes, and silicone polymers; orpoly(bis(fluoroalkoxy)phosphazene), poly(carborane-siloxanes),poly(acrylonitrile-butadiene), poly(1-butene),poly(chlorotrifluoroethylene-vinylidene fluoride) copolymers, poly(ethylvinyl ether), poly(vinylidene fluoride), poly(vinylidenefluoride-hexafluoropropylene)copolymer, elastomeric compositions ofpolyvinylchloride (PVC), polysulfone, polycarbonate,polymethylmethacrylate (PMMA), polytetrafluoroethylene,polydimethylsiloxane (PDMS), and blends thereof.
 19. A method for makinga microfluidic device comprising: providing a microchannel having avalve seat therein; providing a film overlaying the valve seat so as toblock fluid flow when the film is seated directly on top of the valveseat; and providing a mechanism for deflecting the film away from thevalve seat upon actuation, the mechanism comprising: a fluid reservoirfluidly connected to the valve film, an actuator film having aconductive coating thereon covering an opening of the fluid reservoir,wherein the actuator and the valve films are fluidly connected; and afixed electrode opposing and separated from the conductive coating by agap.
 20. The method of claim 19, wherein the conductive coating is acontinuous blanket coating or is patterned by micro-fabrication.
 21. Themethod of claim 19, wherein the fluid reservoir is fluidly connected tothe valve film by a channel.
 22. The method of claim 19, wherein thefluid reservoir is placed in a different physical location than thevalve film to physically separate the location of the actuator film andvalve film, and fluidly connected to both the actuator film and thevalve film by fluidic channels.
 23. The method of claim 19, whereininlet and outlet channels are connected to the fluid reservoir.
 24. Themethod of claim 19, wherein the fluid reservoir is hermetically sealed.25. The method of claim 19, wherein the area of the fluid reservoircovered by the coated film is larger than the area of the fluidreservoir that is in direct fluid contact with the first film.
 26. Themethod of claim 19, wherein at least one of the actuator film or thevalve film is made of an elastomeric polymer.
 27. The method of claim26, wherein the elastomeric polymer is selected from the groupconsisting of polyisoprene, polybutadiene, polychloroprene,polyisobutylene, poly(styrene-butadiene-styrene), the polyurethanes, andsilicone polymers; or poly(bis(fluoroalkoxy)phosphazene),poly(carborane-siloxanes), poly(acrylonitrile-butadiene),poly(1-butene), poly(chlorotrifluoroethylene-vinylidene fluoride)copolymers, poly(ethyl vinyl ether), poly(vinylidene fluoride),poly(vinylidene fluoride-hexafluoropropylene)copolymer, elastomericcompositions of polyvinylchloride (PVC), polysulfone, polycarbonate,polymethylmethacrylate (PMMA), polytetrafluoroethylene,polydimethylsiloxane (PDMS), and blends thereof.